This invention relates generally to a vaccine testing system and method of determining the extent of temperature-induced damage in liquids, and in particular, liquid vaccines.
Freeze-sensitive vaccine preparations can potentially be damaged by freezing during storage and transport from their point of manufacture to their ultimate destination, this route sometimes being referred to as the pharmaceutical “cold chain.”
Vaccines of various kinds employ the use of an adjuvant to enhance immunogenicity. This adjuvant, which could be, for example, micro-particulate aluminum hydroxide or aluminum phosphate, may be coated with a lattice of antigen. When thus attached, the antigen and adjuvant can reduce the dosage necessary to vaccinate, and thus extend vaccine supplies to ensure that more people can be vaccinated. However, if a vial of such a vaccine is frozen, the lattice of antigen may be removed from the adjuvant particles, and the antigen-adjuvant combination may be unable allow vaccinations at low dosages and, therefore, may be unusable.
The previously frozen adjuvant particles often agglomerate into larger clusters. This agglomeration is the basis for two current methods of determining whether an adjuvant-containing vaccine has been frozen previously. The first method is by phase-contrast microscopy, wherein the agglomerated adjuvant is clearly visible and distinguishable from non-agglomerated adjuvant. The second method is called the “shake test”. The “shake test” relies on the faster sedimentation rate of the agglomerated adjuvant particles. The test vial and a known, reference frozen vial are shaken and placed side-by-side. The health worker then watches the two vials until he or she can say for certain whether or not the reference frozen vial is clarifying faster than the test vial. For example, ten and twenty dose vials can be tested in this manner in a matter of several minutes, but a one and two dose vial can take significantly longer before a reliable judgment can be made.
Although shown to be effective, these two methods can potentially have shortcomings. Because vaccines may be delivered to people in the poorest and most remote areas of the world, use of phase contrast microscopy may be impractical for wide use because of the cost and maintenance of a microscope.
The “shake test” is free and effective when carried out properly, but may also be prone to human error. If the health worker is impatient, he or she may not wait long enough to make a reliable judgment about whether a vaccine has been previously frozen or not, raising the likelihood of a false positive. The worker may also neglect to completely freeze the control vial, thereby potentially increasing the likelihood of a false negative. Neither the “shake test” nor phase-contrast microscopy is quantitative, capable of producing a number that can be used to compare a numerical value of one vial versus another.
One method attempting to resolve this problem has been to use freeze indicators. These indicators would provide a calibrated external indicator that a freezing event had taken place. Although these remain important components of the pharmaceutical cold chain, they may not be designed nor have the ability to determine the extent to which vaccine has actually been damaged by freezing temperatures.